ClinVar

In a Korean family with HPT-JT syndrome (145001), Moon et al. (2005) identified a germline mutation in intron 2 of the HRPT2 gene, IVS2-1G-A. RT-PCR and sequencing of the transcripts revealed that this splicing mutation generated alternative splicing errors leading to the formation of 2 different transcripts, one with exon 3 deleted, the other lacking the first 23 bp of exon 3 due to the use of an internal splice acceptor in exon 3. Translation of both transcripts resulted in premature termination. In addition to this germline mutation, Moon et al. (2005) detected 2 somatic mutations of HRPT2 in malignant parathyroid tumors from the affected individuals. The proband carried a 1-bp deletion in exon 1, 85delG, that was predicted to cause premature termination of the protein (607393.0014). The proband's father carried an 18-bp in-frame deletion, 13_30delCTTAGCGTCCTGCGACAG, also in exon 1 (607393.0015). Moon et al. (2005) noted that to the time of their report, all inactivating somatic mutations in HRPT2 have occurred in exon 1.